Guided bone regeneration (GBR) utilizing eggshell membrane (ESM) as a potential biomaterial for dental implant therapy augmentation was explored in this study. ESM, an environmentally friendly waste product, possesses collagen-rich characteristics. The biocompatibility and histological responses of ESM were investigated in a rat model. Twelve young adult Wistar rats were used in this study. ESM samples were implanted in subcutaneous and intramuscular pockets, and samples were collected at 48 hours, 4 weeks, and 8 weeks post-implantation. Histological analysis revealed the changes in ESM over time. Results showed that ESM maintained its structural integrity, induced a moderate cellular response, and exhibited slow degradation, indicating potential biocompatibility. However, the lack of organized collagen arrangement in ESM led to the formation of irregular and polymorphic spaces, allowing cell migration. Encapsulation of ESM by newly proliferating collagen fibers and multinucleated giant cells was observed at later time points, indicating a foreign body reaction. Crosslinking might improve its performance as a separation membrane, as it has the potential to resist enzymatic degradation and enhance biomechanical properties. In conclusion, ESM demonstrated biocompatibility, slow degradation, and lack of foreign body reaction. While not suitable as a complete separation membrane due to irregular collagen arrangement, further research involving crosslinking could enhance its properties, making it a viable option for guided bone regeneration applications in dental implant therapy. This study highlights the potential of repurposing waste materials for medical purposes and underscores the importance of controlled collagen structure in biomaterial development.